BURNS RESEARCH IN THE NETHERLANDS – A
COMBINED EFFORT
Esther Middelkoop, Director of Research,
Dutch Burn Centres
PO box 1015, 1940 EA Beverwijk, The Netherlands
Since 1997 the three Burn Centres in the Netherlands
have collaborated in the field of research. Together they provide expert
clinical care for approximately 500 patients each year. Outpatient visits
of new patients amount to approximately 1000 on a yearly basis.
Although we are a relatively small group in a field of research that
does not have a very long history (the first burn centre was established
in the Netherlands only thirty years ago) we are very ambitious to improve
the final outcome of wound healing for burn victims in the decades to
come.
Our research is focused on the final goal of ‘Scarless Healing’
for burn victims. To reach progress in the treatment of clinical burn
patients, this goal needs to be defined in specific research projects,
with less ambitious goals, but nevertheless contributing to the desired
end point.
Unfortunately, clinical products that promote scarless healing are still
scarce at the moment. For this reason, we try to contribute to the development
of such products by performing experimental studies in in vitro and
in vivo wound healing models,1 as well as participating in
clinical trials.
Tissue engineered
skin
Since the developments of concepts on skin substitutes by Yannas and Burke,2
this field of research has been of great interest to burn surgeons and
researchers. One of the great medical problems associated with burns is
the extensive scarring after healing of full thickness burns. Our research
in this area over the last several years has been focused on the design
and testing of a dermal substitute, as well as on methodology in order
to demonstrate clinical effectiveness.3 The present situation
is that a ‘simple’ biomaterial alone seems to have only limited
effectiveness in scar prevention. Therefore, current and future research
will make use of bio-engineered concepts to try and direct wound healing
processes towards skin regeneration rather than scarring.
The start of Dr Magda Ulrich in our lab in 2001 marked the start of a
more molecular approach to the research questions. This resulted in several
new findings, on which she presented an overview during one of the plenary
sessions of the 2003 ETRS annual meeting in Amsterdam. In short, we hypothesized
that different fibroblast phenotypes, originating from different tissues
such as dermis or subcutaneous fat, would contribute importantly to the
outcome of wound healing. This gained strength by the discovery that mRNA’s
of many relevant enzymes, such as members of the MMP family and enzymes
involved in collagen synthesis and cellular migration, were differentially
expressed in different subsets of fibroblasts (see illustration in Fig.1).4
It is my believe that this type of knowledge will lead us to a tailor-made
design of the tissue engineered products of the future.
Control of
inflammation
In acute wounds the level of inflammation can be very high, and of another
nature than the inflammatory process in chronic wound healing. It is a
long standing hypothesis that the level of inflammation in burns should
be reduced in order to reach a better quality of healing. To reach this
one of our research projects focuses on the reduction of local inflammatory
processes by the administration of liposomes containing immunosuppressants
such as prednisolone-phosphates.
Microbiology
It is common knowledge that burn wounds are easily colonized by bacteria.
One of the more problematic species is Staphylococcus Aureus, which is
associated with disturbed wound healing. A recent study in one of our
burn centres showed that 35% of the admitted patients in a burn center
carried S. Aureus upon admission, and 95% of these patients showed colonization
of their wounds with the same species. In 78% of the cases, the colonizing
strain was the same as the one carried in nose or throat at admission.5
This study also showed that intensive isolation measures were indeed effective
in preventing cross-colonization.
Figure 1. Altered balance of collagen degradation-capacity
© Research Depart. Burn Centers, The Netherlands
Microcirculation
The detection of presence or absence of blood circulation is of high diagnostic
value in determining burn depth.6 We attempt to include this
technique in routine burn care, as well as a quantitative tool in burn
research projects.
Psychosocial implications
of burns
To date the life of extensively burned persons may be saved. However,
these individuals may be faced with severe physical limitations in functional
and aesthetic perspective. Our psychosocial research group tries to understand
and predict the psychosocial impact of a burn injury. Post-traumatic Stress
Disorder or depression may develop as a reaction to the burn accident
itself, but also the painful treatments may contribute to these disorders.
The need for psychosocial care following burn injuries was recently investigated
in the Dutch and several Belgian Burn Centres.7–9 Results of these
studies are described in the thesis of Dr Nancy van Loey.10
Epidemiology
Good research needs qualitative and quantitative data. As stated, the
research history in burns is rather young. Therefore quantitative data
on treatment outcome are not easy to find. It is our ambition to protocolize
not only our treatment regimes, but also our registration regimes. Evaluation
of burn research would become much easier if we could compare present
data of new treatment modalities to an up-to-date and extensive database
on outcome of current burn protocols.
From left to right:
Dr Esther Middelkoop, Director of Research, Linda Reijnen, research technician,
Drs Antoon van den Bogaerdt, PhD student, Dr Magda Ulrich, senior scientist,
head of laboratory,
and Michelle Verkerk, research technician.
References
- Middelkoop E, van den Bogaerdt AJ, Lamme, EN, Hoekstra
MJ, Brandsma K, Ulrich MMW. Porcine wound models for skin substitution
and burn treatment. Biomaterials. 25 (2004), 1559–1567.
- Yannas IV, Burke JF. Design of an artificial skin.
I. Basic design principles. J Biomed Mater Res. 1980 Jan; 14(1):
65–81.
- Van Zuijlen, PPM. Perspectives on burn scar evaluation
and artificial skin. University of Amsterdam, thesis, 2002. ISBN:
90–9015126–5.
- Van den Bogaerdt AJ, El Ghalbzouri A, Hensbergen P,
Reijnen L, Verkerk M, Kroon-Smits M, Middel-koop E, and Ulrich MMW.
Biochem. Biophys. Res. Commun. 315 (2004), 428–433.
- Kooistra-Smid M, van Dijk S, Beerthuizen B, Vogels
W, van Zwet T, van Belkum A, and Verbrugh H. Molecular epidemiology
of Staphylococcus aureus colonization in a burn center. Burns.
30, 2004, 27–33.
- Kloppenberg FW, Beerthuizen GI, and ten Duis HJ. Perfusion
of burn wounds assessed by laser doppler imaging is related to burn
depth and healing time. Burns. 2001 Jun; 27(4): 359–63.
- Van Loey NE, Maas CJ, Faber AW, Taal LA. Predictors
of chronic posttraumatic stress symptoms following burn injury: results
of a longitudinal study. J Trauma Stress. 2003 Aug; 16(4):
361–9.
- Van Loey NE, Van Son MJ. Psychopathology and psychological
problems in patients with burn scars: epidemiology and management. Am
J. Clin Dermatol. 2003; 4(4): 245–272.
- Van Loey NE, Faber AW, Taal LA. Do burn patients need
burn specific multidisciplinary outpatient aftercare: research results.
Burns. 2001 Mar; 27(2): 103–110.
- Van Loey NEE. Beyond burns, identification and
impact of posttraumatic stress disorder. University of Utrecht,
thesis, 2003. ISBN 90 393 3452 8.
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